Three separate influenza pandemics have emerged in the human population since 1918, each characterized by viruses that lack N-linked glycosylation sites on the globular head of the hemagglutinin protein. In contrast, recent non-pandemic isolates have acquired such sites. Here we constructed isogenic viruses containing differing numbers of additional N-linked glycosylation sites to assess the impact on the host immune response. These studies show that mice infected with a glycosylated virus remain susceptible to challenge with a non-glycosylated virus, glycosylated viruses elicit an inferior immune response, and in this context T-cell pathology and death may occur. We conclude from these data that glycosylation leads to a lack of neutralization coupled with a robust T-cell response. Specifically, glycosylation of HA seems to shield neutralizing antibody epitopes while leaving T-cell epitopes unaffected. These results may be particularly significant in the context of the recent influenza pandemic.
","abstract_html":"<p>Three separate influenza pandemics have emerged in the human population since 1918, each characterized by viruses that lack N-linked glycosylation sites on the globular head of the hemagglutinin protein. In contrast, recent non-pandemic isolates have acquired such sites. Here we constructed isogenic viruses containing differing numbers of additional N-linked glycosylation sites to assess the impact on the host immune response. These studies show that mice infected with a glycosylated virus remain susceptible to challenge with a non-glycosylated virus, glycosylated viruses elicit an inferior immune response, and in this context T-cell pathology and death may occur. We conclude from these data that glycosylation leads to a lack of neutralization coupled with a robust T-cell response. Specifically, glycosylation of HA seems to shield neutralizing antibody epitopes while leaving T-cell epitopes unaffected. These results may be particularly significant in the context of the recent influenza pandemic.</p>","abstract_has_math":false,"creators":["Wanzeck, Keith C."],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Thesis","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Jonathan A. McCullers Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-05-01T07:00:00Z","date_published":"2010-05-01T07:00:00Z","updated_at":"2026-07-24T05:00:17Z","subjects":["glycosylation","hemagglutinin","influenza","neutralizing antibodies","T-cells","Diseases","Influenza Humans","Medical Molecular Biology","Medical Sciences","Medicine and Health Sciences","Virus Diseases"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/280","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Jonathan A. McCullers Ph.D."]},{"key":"dc:creator","label":"Author","values":["Wanzeck, Keith C."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-06-17T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["glycosylation","hemagglutinin","influenza","neutralizing antibodies","T-cells","Diseases","Influenza Humans","Medical Molecular Biology","Medical Sciences","Medicine and Health Sciences","Virus Diseases"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/280"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Three separate influenza pandemics have emerged in the human population since 1918, each characterized by viruses that lack N-linked glycosylation sites on the globular head of the hemagglutinin protein. In contrast, recent non-pandemic isolates have acquired such sites. Here we constructed isogenic viruses containing differing numbers of additional N-linked glycosylation sites to assess the impact on the host immune response. These studies show that mice infected with a glycosylated virus remain susceptible to challenge with a non-glycosylated virus, glycosylated viruses elicit an inferior immune response, and in this context T-cell pathology and death may occur. We conclude from these data that glycosylation leads to a lack of neutralization coupled with a robust T-cell response. Specifically, glycosylation of HA seems to shield neutralizing antibody epitopes while leaving T-cell epitopes unaffected. These results may be particularly significant in the context of the recent influenza pandemic.
"]},{"key":"dc:title","label":"Title","values":["Glycan Shielding of the Influenza Virus Hemagglutinin Elicits Evasion of the Adaptive Immune Response and T-Cell-Driven Pathology"]}]}],"canonical_facts":{"dc:contributor":["Jonathan A. McCullers Ph.D."],"dc:creator":["Wanzeck, Keith C."],"dc:date.available":["2016-06-17T07:00:00Z"],"dc:description.abstract":["Three separate influenza pandemics have emerged in the human population since 1918, each characterized by viruses that lack N-linked glycosylation sites on the globular head of the hemagglutinin protein. In contrast, recent non-pandemic isolates have acquired such sites. Here we constructed isogenic viruses containing differing numbers of additional N-linked glycosylation sites to assess the impact on the host immune response. These studies show that mice infected with a glycosylated virus remain susceptible to challenge with a non-glycosylated virus, glycosylated viruses elicit an inferior immune response, and in this context T-cell pathology and death may occur. We conclude from these data that glycosylation leads to a lack of neutralization coupled with a robust T-cell response. Specifically, glycosylation of HA seems to shield neutralizing antibody epitopes while leaving T-cell epitopes unaffected. These results may be particularly significant in the context of the recent influenza pandemic.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/280"],"dc:subject":["glycosylation","hemagglutinin","influenza","neutralizing antibodies","T-cells","Diseases","Influenza Humans","Medical Molecular Biology","Medical Sciences","Medicine and Health Sciences","Virus Diseases"],"dc:title":["Glycan Shielding of the Influenza Virus Hemagglutinin Elicits Evasion of the Adaptive Immune Response and T-Cell-Driven Pathology"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T05:00:17Z"}